With the US population aging, it is important to find novel dental biomaterials that will promote periodontal regeneration, and translate these to clinical practice. As both a dentist and materials scientist, the applicant is in a position to brige the gap between biomaterials development. and their application in patient care using nanotechnology, tissue engineering and clinical knowledge. The purpose of this award is to provide the principal investigator extensive training in cellular and molecular biology, skeletal biology, and translational research with an emphasis on periodontal tissue regeneration. The experiments in this application have been designed to incorporate new methodologies, and will be guided by a multidisciplinary team of experts who will provide the required training to advance Dr. Bottino's scientific technical and analytic skills. The principal investigator's ultimae goal is to become a productive and independent clinician-scientist who can secure federal funding to sponsor an independent research program. The central hypothesis of the proposed research is that a multilayer membrane capable of stimulating the regeneration of various tissue types in a location specific manner, through the addition of calcium phosphate and fibroblast growth factor-2 (CaP/FGF2) and FGF2, will lead to alveolar and periodontal tissue regeneration in the appropriate locations. The literature indicates that no single implantable biomaterial can consistently guide the coordinated growth and development of multiple tissue types, especially in very large periodontal defects. Thus, there is a critical need to develop regenerative therapies to promote oral and craniofacial tissue regeneration and reconstruction. The specific aims of the proposed research are (1) To use an in vitro assay model to maximize the tissue-specific regenerative capacity of the multilayered implant surface layers, (2) To assess the effectiveness of CaP/FGF2 on bone regeneration in an alveolar defect using an in vivo canine model, and (3) To assess the effectiveness of the multilayered implant to regenerate soft and mineralized tissues in a location-specific manner using an in vivo canine model. The principal investigator has devised a comprehensive career development plan that includes formal coursework, laboratory guidance to cover intensive cell and molecular biology training, as well as in vivo techniques combined with a diverse set of bone/periodontal tissue regeneration related analyses under the supervision of his mentoring team. Collectively, the K08 award has the capacity to provide the resources and training needed to give the applicant the foundation and critical theoretical and practical means to become a highly qualified clinician-scientist who can translate his knowledge of biomaterials to clinical practice.